Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos

BackgroundPlacebo groups are used in randomised clinical trials (RCTs) to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.Methods and FindingsWe conducted a content analysis of 45 Participant Information Leaflets (PILs) using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database). Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%), but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001) and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001) or adverse effects (4 vs. 39, p<001). 8 PILs (18%) explicitly stated that the placebo treatment was either undesirable or ineffective.ConclusionsPILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled trials

Ground State Energy of the One-Dimensional Discrete Random Schr\"{o}dinger Operator with Bernoulli Potential

In this paper, we show the that the ground state energy of the one dimensional Discrete Random Schroedinger Operator with Bernoulli Potential is controlled asymptotically as the system size N goes to infinity by the random variable \ell_N, the length the longest consecutive sequence of sites on the lattice with potential equal to zero. Specifically, we will show that for almost every realization of the potential the ground state energy behaves asymptotically as $\frac{\pi^2}{\ell_N+1)^2}$ in the sense that the ratio of the quantities goes to one

Maternal pregnancy vitamin D supplementation increases offspring bone formation in response to mechanical loading : findings from a MAVIDOS trial sub-study

The Maternal Vitamin D Osteoporosis (MAVIDOS) trial reported higher total body bone mineral content in winter-born infants of mothers receiving vitamin D supplementation [1000 IU/day cholecalciferol] compared with placebo from 14 weeks gestation until delivery. This sub-study aimed to determine whether antenatal vitamin D supplementation altered postnatal bone formation in response to mechanical stimulation. Thirty-one children born to MAVIDOS participants randomised to either placebo (n=19) or cholecalciferol (n=12) were recruited at age 4-5 years. Children received whole body vibration (WBV) for 10 minutes on 5 consecutive days. Fasting blood samples for bone homeostasis, 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and bone turnover markers (Pro-collagen Type 1 N-terminal propeptide, P1NP; Cross-linked C-telopeptide of Type I Collagen, CTX) were collected pre-WBV and on day 8 (D8). Mean changes (D) in P1NP (ng/ml) between baseline and D8 in the vitamin-D intervention and placebo groups were 40.6 and -92.6 respectively and mean changes (Δ) in CTX (ng/ml) were 0.034 (intervention) and -0.084 (placebo) respectively. Between-group DP1NP difference was 133.2ng/ml [95% CI 0.4, 266.0; p=0.049] and ΔCTX 0.05ng/ml (95% CI -0.159, 0.26ng/mL; p=0.62). Antenatal vitamin-D supplementation resulted in increased P1NP in response to WBV, suggesting early life vitamin D supplementation increases the anabolic response of bone to mechanical loading in children

Magnetic order in spin-1 and spin-3/2 interpolating square-triangle Heisenberg antiferromagnets

Using the coupled cluster method we investigate spin-$s$ $J_{1}$-$J_{2}'$ Heisenberg antiferromagnets (HAFs) on an infinite, anisotropic, triangular lattice when the spin quantum number $s=1$ or $s=3/2$. With respect to a square-lattice geometry the model has antiferromagnetic ($J_{1} > 0$) bonds between nearest neighbours and competing ($J_{2}' > 0$) bonds between next-nearest neighbours across only one of the diagonals of each square plaquette, the same one in each square. In a topologically equivalent triangular-lattice geometry, we have two types of nearest-neighbour bonds: namely the $J_{2}' \equiv \kappa J_{1}$ bonds along parallel chains and the $J_{1}$ bonds producing an interchain coupling. The model thus interpolates between an isotropic HAF on the square lattice at $\kappa = 0$ and a set of decoupled chains at $\kappa \rightarrow \infty$, with the isotropic HAF on the triangular lattice in between at $\kappa = 1$. For both the $s=1$ and the $s=3/2$ models we find a second-order quantum phase transition at $\kappa_{c}=0.615 \pm 0.010$ and $\kappa_{c}=0.575 \pm 0.005$ respectively, between a N\'{e}el antiferromagnetic state and a helical state. In both cases the ground-state energy $E$ and its first derivative $dE/d\kappa$ are continuous at $\kappa=\kappa_{c}$, while the order parameter for the transition (viz., the average on-site magnetization) does not go to zero on either side of the transition. The transition at $\kappa = \kappa_{c}$ for both the $s=1$ and $s=3/2$ cases is analogous to that observed in our previous work for the $s=1/2$ case at a value $\kappa_{c}=0.80 \pm 0.01$. However, for the higher spin values the transition is of continuous (second-order) type, as in the classical case, whereas for the $s=1/2$ case it appears to be weakly first-order in nature (although a second-order transition could not be excluded).Comment: 17 pages, 8 figues (Figs. 2-7 have subfigs. (a)-(d)

A Detailed Investigation into Low-Level Feature Detection in Spectrogram Images

Being the first stage of analysis within an image, low-level feature detection is a crucial step in the image analysis process and, as such, deserves suitable attention. This paper presents a systematic investigation into low-level feature detection in spectrogram images. The result of which is the identification of frequency tracks. Analysis of the literature identifies different strategies for accomplishing low-level feature detection. Nevertheless, the advantages and disadvantages of each are not explicitly investigated. Three model-based detection strategies are outlined, each extracting an increasing amount of information from the spectrogram, and, through ROC analysis, it is shown that at increasing levels of extraction the detection rates increase. Nevertheless, further investigation suggests that model-based detection has a limitation—it is not computationally feasible to fully evaluate the model of even a simple sinusoidal track. Therefore, alternative approaches, such as dimensionality reduction, are investigated to reduce the complex search space. It is shown that, if carefully selected, these techniques can approach the detection rates of model-based strategies that perform the same level of information extraction. The implementations used to derive the results presented within this paper are available online from http://stdetect.googlecode.com

Life after charge noise: recent results with transmon qubits

We review the main theoretical and experimental results for the transmon, a superconducting charge qubit derived from the Cooper pair box. The increased ratio of the Josephson to charging energy results in an exponential suppression of the transmon's sensitivity to 1/f charge noise. This has been observed experimentally and yields homogeneous broadening, negligible pure dephasing, and long coherence times of up to 3 microseconds. Anharmonicity of the energy spectrum is required for qubit operation, and has been proven to be sufficient in transmon devices. Transmons have been implemented in a wide array of experiments, demonstrating consistent and reproducible results in very good agreement with theory.Comment: 6 pages, 4 figures. Review article, accepted for publication in Quantum Inf. Pro

Summer CO2 evasion from streams and rivers in the Kolyma River basin, north-east Siberia

Inland water systems are generally supersaturated in carbon dioxide (CO2) and are increasingly recognized as playing an important role in the global carbon cycle. The Arctic may be particularly important in this respect, given the abundance of inland waters and carbon contained in Arctic soils; however, a lack of trace gas measurements from small streams in the Arctic currently limits this understanding.We investigated the spatial variability of CO2 evasion during the summer low-flow period from streams and rivers in the northern portion of the Kolyma River basin in north-eastern Siberia. To this end, partial pressure of carbon dioxide (pCO2) and gas exchange velocities (k) were measured at a diverse set of streams and rivers to calculate CO2 evasion fluxes. We combined these CO2 evasion estimates with satellite remote sensing and geographic information system techniques to calculate total areal CO2 emissions. Our results show that small streams are substantial sources of atmospheric CO2 owing to high pCO2 and k, despite being a small portion of total inland water surface area. In contrast, large rivers were generally near equilibrium with atmospheric CO2. Extrapolating our findings across the Panteleikha-Ambolikha sub-watersheds demonstrated that small streams play a major role in CO2 evasion, accounting for 86% of the total summer CO2 emissions from inland waters within these two sub-watersheds. Further expansion of these regional CO2 emission estimates across time and space will be critical to accurately quantify and understand the role of Arctic streams and rivers in the global carbon budget

An assessment of Evans' unified field theory I

Evans developed a classical unified field theory of gravitation and electromagnetism on the background of a spacetime obeying a Riemann-Cartan geometry. This geometry can be characterized by an orthonormal coframe theta and a (metric compatible) Lorentz connection Gamma. These two potentials yield the field strengths torsion T and curvature R. Evans tried to infuse electromagnetic properties into this geometrical framework by putting the coframe theta to be proportional to four extended electromagnetic potentials A; these are assumed to encompass the conventional Maxwellian potential in a suitable limit. The viable Einstein-Cartan(-Sciama-Kibble) theory of gravity was adopted by Evans to describe the gravitational sector of his theory. Including also the results of an accompanying paper by Obukhov and the author, we show that Evans' ansatz for electromagnetism is untenable beyond repair both from a geometrical as well as from a physical point of view. As a consequence, his unified theory is obsolete.Comment: 39 pages of latex, modified because of referee report, mistakes and typos removed, partly reformulated, taken care of M.W.Evans' rebutta

Determinants of the maternal 25-hydroxyvitamin D response to vitamin D supplementation during pregnancy

Context: Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response.Objective: We assessed which maternal and environmental characteristics were associated with 25(OH)D after supplementation with cholecalciferol.Design: Within-randomization-group analysis of participants in the Maternal Vitamin D Osteoporosis Study trial of vitamin D supplementation in pregnancy.Setting: Hospital antenatal clinics.Participants: A total of 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks of gestation, maternal anthropometry, health, and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks.Interventions: 1000 IU/d of cholecalciferol or matched placebo from 14 weeks of gestation until delivery.Main Outcome Measure: 25(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison).Results: 25(OH)D at 34 weeks of gestation was higher in the women randomized to vitamin D (mean [SD], 67.7 [21.3] nmol/L) compared with placebo (43.1 [22.5] nmol/L; P &lt; .001). In women randomized to cholecalciferol, higher pregnancy weight gain from 14 to 34 weeks of gestation (kg) (? = ?0.81 [95% confidence interval ?1.39, ?0.22]), lower compliance with study medication (%) (? = ?0.28 [?0.072, ?0.48]), lower early pregnancy 25(OH)D (nmol/L) (? = 0.28 [0.16, 0.40]), and delivery in the winter vs the summer (? = ?10.5 [?6.4, ?14.6]) were independently associated with lower 25(OH)D at 34 weeks of gestation.Conclusions: Women who gained more weight during pregnancy had lower 25(OH)D in early pregnancy and delivered in winter achieved a lower 25(OH)D in late pregnancy when supplemented with 1000 IU/d cholecalciferol. Future studies should aim to determine appropriate doses to enable consistent repletion of 25(OH)D during pregnancy.<br/

Software engineering techniques for the development of systems of systems

This paper investigates how existing software engineering techniques can be employed, adapted and integrated for the development of systems of systems. Starting from existing system-of-systems (SoS) studies, we identify computing paradigms and techniques that have the potential to help address the challenges associated with SoS development, and propose an SoS development framework that combines these techniques in a novel way. This framework addresses the development of a class of IT systems of systems characterised by high variability in the types of interactions between their component systems, and by relatively small numbers of such interactions. We describe how the framework supports the dynamic, automated generation of the system interfaces required to achieve these interactions, and present a case study illustrating the development of a data-centre SoS using the new framework